Progesterone induced immune modulation during pregnancy – supplemental research in COVID-19

怀孕期间黄体酮诱导的免疫调节 — COVID-19 的补充研究

• 批准号: 10200397
• 负责人: Sing Sing Way
• 金额: $ 48.88万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-04 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200397
• 关键词: 2019-nCoV; Address; Age; Area; Biology; COVID-19; COVID-19 severity; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Data; Cohort Studies; Complement; Data; Disease; Enrollment; Exposure to; Fetal Death; High Prevalence; Immune; Immune response; Immunity; Immunoglobulin G; Immunoglobulin M; Immunologics; Immunology; Infection; Institution; Intervention; Intervention Trial; Investigation; Knowledge; Logistics; Maternal Mortality; Maternal antibody; Maternally-Acquired Immunity; Metadata; Mothers; Parents; Patients; Pennsylvania; Perinatology; Persons; Phenotype; Population; Postpartum Period; Pre-Eclampsia; Predisposition; Pregnancy; Pregnancy Trimesters; Pregnant Women; Premature Birth; Progesterone; Research; Research Infrastructure; Risk; SARS-CoV-2 infection; SARS-CoV-2 positive; Second Pregnancy Trimester; Serology test; Severities; Severity of illness; Specimen; Time; Translational Research; Umbilical Cord Blood; Universities; Woman; Work; adjudication; adverse pregnancy outcome; clinical phenotype; cohort; design; disorder risk; embryo/fetus antigen; ethnic diversity; fetal; high risk population; immunoregulation; innovation; insight; maternal comorbidity; maternal morbidity; novel; novel coronavirus; obstetric outcomes; pandemic disease; parity; patient population; pregnant; preventive intervention; prospective; racial diversity; recruit; reproductive; reproductive outcome; respiratory virus; severe COVID-19; social health determinants; symptomatology; translational study; virology

Project Summary: Despite pandemic spread of the novel coronavirus, COVID-19, significant knowledge gaps remain especially for Center for Disease Control designated high risk populations such as pregnant women. Of high clinical importance is the susceptibility of pregnant women to infection, the direct risk to the mother and the indirect impact of disease severity (including preterm delivery and fetal death) on the pregnancy. While much research is being pursued from translational research to intervention trials for COVID-19, pregnant women are almost universally excluded from intervention and observational trials. Research in pregnant women is of the highest priority. The ability to understand which pregnant women are at risk for severe COVID-19 disease, weeks if not months prior to clinical symptomatology, could provide novel and important windows for preventative interventions to limit maternal morbidity and mortality. Additionally, if clinical data emerges that the majority of pregnant women may actually be more tolerant of SARS-CoV-2 compared to other respiratory viruses, understanding the immunological changes of pregnancy may provide insights as to ways to modulate disease risk in non-pregnant populations. To address all of these gaps in knowledge, large maternal cohorts with biospecimens and detailed phenotyping in areas of high prevalence of COVID-19 are required. The established investigative team and research infrastructure for two active maternal cohorts designed for prospective analysis of maternal immunity during pregnancy (R01-A1145840) can now be leveraged to investigate deep immune phenotyping of pregnant women prior to acquisition of COVID-19. We will be able to investigate how different immune phenotypes predict COVID-19 infection in pregnant women. Complementing the existing expertise in perinatology and immunology for the parent RO1, this study add the immunology and virology expertise at the University of Pennsylvania. We propose to investigate the following three scientifically important aims: 1) whether maternal immune profiles are associated with acquisition and severity of COVID19 in pregnant women; 2) whether immune profiles in pregnant women with active COVID19 are similar to non-pregnant women with similar disease severity and 3) whether immune profiles in the 2nd trimester of pregnancy are associated with adverse reproductive outcomes. All women enrolled will have extensive metadata collected with adjudication of COIVD- 19 status and severity as well as detailed clinical phenotyping of obstetrical outcomes. Deep immune phenotyping will provide innovative and rigorous investigation of innate and adaptive immune states during pregnancy and will be interrogated regarding their association with COVID19 phenotypes. We will also investigate the presence of maternal antibodies (IgG and IgM against SARS-CoV-2) at the same time point as immune profiling. We have the necessary expertise, the research infrastructure and the patient population to complete the proposed study in the 2 year time line with a 400 person cohort. This study address many significant gaps in knowledge including essential questions regarding the immune biology in pregnancy.

项目概述：尽管新型冠状病毒新冠肺炎在全球大流行，但仍存在巨大的知识差距 特别适用于疾病控制中心指定的高危人群，如孕妇。的 高度临床重要性是孕妇对感染的易感性，对母亲和 疾病严重程度(包括早产和胎儿死亡)对妊娠的间接影响。虽然有很多 新冠肺炎的研究正在从翻译研究到干预试验，孕妇 几乎所有人都排除在干预和观察性试验之外。对孕妇的研究是 最高优先级。了解哪些孕妇有患严重新冠肺炎疾病的风险的能力 如果不是在临床症状出现前几个月，可能会为预防提供新的重要窗口 限制孕产妇发病率和死亡率的干预措施。此外，如果临床数据显示大多数 与其他呼吸道病毒相比，孕妇实际上可能对SARS-CoV-2更耐受， 了解妊娠的免疫学变化可能会为调节疾病的方式提供见解 非怀孕人群中的风险。为了解决所有这些知识上的差距，有大量母亲参加 需要在新冠肺炎高发地区进行生物检疫和详细的表型分析。已建立的 为前瞻性分析而设计的两个活跃孕产妇队列的调查小组和研究基础设施 孕期母体免疫力(R01-A1145840)现在可以用来研究深度免疫 收购新冠肺炎前孕妇的表型分析。我们将能够调查有何不同 免疫表型预测孕妇感染新冠肺炎。补充现有的专业知识 对于亲代RO1的围产期和免疫学，这项研究增加了免疫学和病毒学的专业知识 宾夕法尼亚大学。我们建议调查以下三个具有重要科学意义的目标：1) 孕妇的免疫状况与感染柯萨奇病毒19的孕妇的感染和严重程度有关； 患有活动性COVID19的孕妇与患有类似疾病的非孕妇的免疫状况是否相似 疾病严重程度和3)妊娠中期的免疫状况是否与不良反应有关 生殖结果。所有注册的女性将在COIVD裁决时收集广泛的元数据- 19产科结局的状况和严重程度以及详细的临床表型。深度免疫 表型鉴定将提供对先天和获得性免疫状态的创新和严格的研究 并将就它们与COVID19表型的关联进行讯问。我们还将 调查同一时间点是否存在母体抗体(SARS-CoV-2的免疫球蛋白G和免疫球蛋白M) 免疫分析。我们拥有必要的专业知识、研究基础设施和患者群体 在两年的时间线内完成拟议的研究，共400人。这项研究解决了许多重要的问题 知识方面的差距，包括关于怀孕期间免疫生物学的基本问题。